Guideline No. 390-Classification and Management of Endometrial Hyperplasia

Abstract Objective The aim of this guideline is to aid primary care physicians and gynaecologists in the initial evaluation of women with suspected endometrial hyperplasia, to recommend the use of the 2014 World Health Organization classification for endometrial hyperplasia by all health care providers, and to guide the optimal treatment of women diagnosed with endometrial hyperplasia. Intended Users Physicians, including gynaecologists, obstetricians, family physicians, general surgeons, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; medical trainees, including medical students, residents, and fellows; and all other health care providers. Target Population Adult women (18 years and older) presenting with suspected or confirmed endometrial hyperplasia. Options The discussion relates to the medical therapy as well as surgical treatment options for women with and without atypical endometrial hyperplasia. Evidence For this guideline, relevant studies were searched in PubMed, Cochrane Wiley, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials, human subjects, and published since 2000: (endometrial hyperplasia, endometrial intraepithelial neoplasia, endometrial sampling, endometrial curettage, diagnosis) AND (treatment, progestin therapy, surgery, LNG-IUS, aromatase inhibitors, metformin ), AND (obesity). The search was performed in April 2018. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 2152, and 82 studies were included in this review. Validation Methods The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. The interpretation of strong and weak recommendations was also included. The Summary of Findings is available upon request. Benefits, Harms, and/or Costs It is expected that this guideline will benefit women with endometrial hyperplasia. This should guide patient informed consent before both medical and surgical management of this condition. Guideline Update Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. Summary Statements 1In addition to epidemiologic risk factors related to estrogen exposure, intermenstrual bleeding and postmenopausal bleeding are associated with increased risk of endometrial hyperplasia. Endometrial sampling should be carried out as per published algorithms with particular attention to women 40 years or older or with a body mass index of 30 kg/m2 or greater (moderate). 2Since the majority of cases of endometrial hyperplasia without atypia are successfully managed medically, hysterectomy is not considered first-line treatment and surgery is reserved for specific circumstances (moderate). 3A minimally invasive approach to hysterectomy is preferred for endometrial hyperplasia as it decreases perioperative morbidity and mortality (high). 4If hysterectomy is indicated for endometrial hyperplasia without atypia then postmenopausal women should also be offered bilateral salpingo-oophorectomy. This decision is individualized for premenopausal women due to increased mortality and morbidity associated with removal of the ovaries in young women with benign disease (moderate). 5Hysterectomy and bilateral salpingo-oophorectomy are the recommended treatment for atypical endometrial hyperplasia due to the underlying risk of malignancy or progression to endometrial cancer. Retention of the ovaries in premenopausal women may be considered (low). 6There is no evidence to support routine intraoperative frozen section analysis in cases of endometrial hyperplasia (low). 7There is no evidence to support routine lymphadenectomy for atypical endometrial hyperplasia (moderate). 8There is insufficient evidence to support endometrial ablation as first-line surgical treatment for endometrial hyperplasia without atypia (low). 9Endometrial hyperplasia found in endometrial polyps should be treated according to its histologic classification (low). Recommendations 1Health care providers should use the 2014 World Health Organization histopathologic classification of endometrial hyperplasia (strong, low). If endometrial cancer is suspected, endometrial tissue sampling using a Pipelle device in an outpatient setting is the most appropriate first step for diagnosis (strong, high). 2Those with recurrent symptoms of abnormal uterine bleeding after initial observation or medical treatment should be reassessed with an endometrial biopsy (strong, high). 3Patients with endometrial hyperplasia should be assessed for reversible risk factors and receive education and support from their clinicians in order to treat and reverse those conditions (strong, high). 4Patients with endometrial hyperplasia without atypia can be observed. They can be offered hormonal treatment if hyperplasia does not resolve with observation or experience abnormal uterine bleeding (weak, low). 5The levonorgestrel intrauterine system should be used as the first-line treatment for endometrial hyperplasia without atypia due to its effectiveness and favourable side effect profile (strong, high) and due to the fact that it can be kept in place for 5 years in patients showing treatment response (strong, moderate). 6Low-dose oral and injectable progestins remain an acceptable treatment option for women with endometrial hyperplasia with and without atypia desiring an alternative treatment modality (strong, high). For patients on oral progestins, we suggest starting on a low dose for a minimum of 6 months. We suggest that assessment of the endometrium be done mid-therapy as well as 3 weeks after completion of treatment to ensure proper interpretation (strong, very low). 7Surgical treatment of endometrial hyperplasia without atypia should be reserved for patients who do not want to preserve their fertility and experience progression to atypical hyperplasia or carcinoma during follow-up, whose hyperplasia fails to regress after 12 months of medical treatment or relapses after completing treatment with progestins, who continue to experience abnormal uterine bleeding despite treatment, or who decline endometrial surveillance or medical treatment (strong, high). 8If surgery is indicated for endometrial hyperplasia without atypia, the procedure should include total hysterectomy with opportunistic salpingectomy, with or without bilateral oophorectomy depending on menopausal status (strong, moderate). 9Total hysterectomy with bilateral salpingo-oophorectomy is recommended for treatment of atypical hyperplasia in premenopausal and postmenopausal women (strong, moderate). In premenopausal women, ovarian preservation should be discussed (strong, moderate). 10We recommend that subtotal (supracervical) hysterectomy and morcellation be avoided in all cases of endometrial hyperplasia (strong, low).